Contrast Agents and Applications to Assess Tumor Angiogenesis In Vivo by Magnetic Resonance Imaging

Abstract

Angiogenesis plays a key role in the development of cancer and is precondition for tumor growth, invasion and spread. Therefore, numerous angiogenesis inhibitors have been developed, of which some show potential to defeat cancer in preclinical and clinical trials. However, response to antiangiogenic treatments is often delayed and marked by high interindividual variability making a closely mashed and efficient observation of the patient necessary. Therefore, surrogate markers which specifically catch early response to tumor therapy are highly desirable. Functional parameters like relative blood volume, perfusion and vessel permeability can be assessed using T(1) and T(2)*-weighted dynamic contrast-enhanced (DCE) MRI. Various reports are available on this topic but results are controversial. During antiangiogenic therapies some authors describe pronounced changes in blood volume: others find effects only on vessel permeability or perfusion. These conflictive observations can be attributed to the different tumor models, therapies, measurement techniques and contrast agents (CA). Particularly the choice of the optimal CA is considered to be essential for a successful characterization of tumor angiogenesis. Often therapy effects on vessel permeability only become apparent, when blood pool CA are used. This article reviews the current state of DCE and molecular MRI of angiogenesis. Besides a general introduction of the different measurement and postprocessing methods and its previous applications, design, structure and use of different types of CA are the main focus of this article.

Nanoparticles for Imaging: Top or Flop?

“…As positive MR contrast agents (bright on T1), Gd-loaded polymers (e.g. poly-lysine dendrimers, N-(2-hydroxypropyl)methacrylamide (HPMA) -co-polymers)(4) and paramagnetic liposomes (6) as well as very small superparamagentic iron oxide nanoparticles, such as citrate-coated very small superparamagnetic iron oxide nanoparticles (VSOP) (14) were successfully applied in preclinical and/or clinical trials. Unfortunately, none of these agents was finally approved for clinical use.…”

Targeting αvβ3 Integrin: Design and Applications of Mono- and Multifunctional RGD-Based Peptides and Semipeptides

“…(34)). Hydrophilic PEGylated conjugate (140) was found to possess superior in vivo pharmacokinetics with higher tumor-to-blood, tumor-to-liver, tumor-to-muscle, and tumor-to-lung ratios with respect to more lipophilic counterparts (141) and (142). This demonstrated that the chemical nature of the attached beacon moiety can be rationally tuned to tailor the overall biodistribution profile of the radiotracer.…”

“…Optical imaging, in particular fluorescence imaging and magnetic resonance imaging, nicely complements the above mentioned radionuclide-based techniques in "seeing" within the living body and understanding the biological complexities for disease treatment [141]. In the last few years, several research groups have demonstrated the utility of coupling v 3 -directing cyclic RGD peptides to optical-and MRactive molecular beacons for use in noninvasive in vitro, in vivo, and ex vivo imaging of tumor-related angiogenesis.…”

Increase in tumour permeability following TGF-β type I receptor-inhibitor treatment observed by dynamic contrast-enhanced MRI

“…Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is one of the evaluation methods of anti-angiogenic agents, such as anti-VEGF antibody and tyrosine kinase inhibitor, clinically (Morgan et al, 2003;O'Connor et al, 2007) and preclinically (Marzola et al, 2004;Nakamura et al, 2006;Bradley et al, 2009), by calculating pharmacokinetic parameters, including fractional plasma volume (v p ) and the volume transfer constant (K trans ) from the enhancement of tumour signal intensity by gadolinium (Gd) contrast agent (Tozer, 2003;Kiessling et al, 2007). To my knowledge, however, there are no reports to evaluate TbR-I inhibitor by DCE-MRI.…”